Kibat P G, Igari Y, Wheatley M A, Eisen H N, Langer R
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge 02139.
FASEB J. 1990 May;4(8):2533-9. doi: 10.1096/fasebj.4.8.2110539.
A system for the delayed or pulsed release of biologically active substances was achieved by encapsulating liposomes containing the substance of interest inside microcapsules. The microcapsules retain the liposomes but allow controlled diffusion of the active substance when it is released from the liposomes. Furthermore, by coating the liposomes with phospholipase A2 (an enzyme that removes an acyl group from the 2 position of phospholipids) before placing them within the microcapsule, a pulsatile release pattern was achieved both in vitro and in vivo. The time of onset of the pulse as well as the release rate can be controlled by the amount of phospholipase A2, the molecular weight of the poly(L-lysine) that is used to coat the microencapsulated liposomes, and the composition of the phospholipid bilayer membrane. Even at 37 degrees C the system would protect a model enzyme (horseradish peroxidase). When not placed inside the microencapsulated liposomes, the enzyme lost its activity in solution at 37 degrees C in a few days, whereas it retained 40% of the initial activity after 30 days of incubation at 37 degrees C inside the microencapsulated liposomes.
通过将含有目标物质的脂质体包裹在微胶囊内，实现了生物活性物质的延迟或脉冲释放系统。微胶囊保留脂质体，但当活性物质从脂质体中释放时，允许其进行可控扩散。此外，在将脂质体置于微胶囊内之前，用磷脂酶A2（一种从磷脂的2位去除酰基的酶）包被脂质体，在体外和体内均实现了脉冲释放模式。脉冲起始时间以及释放速率可通过磷脂酶A2的量、用于包被微囊化脂质体的聚（L-赖氨酸）的分子量以及磷脂双层膜的组成来控制。即使在37℃时，该系统也能保护一种模型酶（辣根过氧化物酶）。当不置于微囊化脂质体内时，该酶在37℃的溶液中几天内就会失去活性，而在微囊化脂质体内于37℃孵育30天后，它仍保留40%的初始活性。
